Function of PrPC as a copper-binding protein at the synapse

Summary

The prion protein (PrPC) shows cooperative copper binding of the N-terminal octarepeat (PHGGGWGO) ×4. In brain homogenates, PrPC is found in highest concentration in synaptosomal fractions. Mice devoid of PrPC (Prnp0/0 mice) show synaptosomal copper concentrations diminished by 50% as compared to normal mice. PrPC in the synaptic cleft may serve as a copper buffer. Alternatively it may play a role in the reuptake of copper into the presynapse or may be of structural importance for the N-terminus and thus may influence binding of PrPC to other proteins.